Reports:who2006
WHO報告書2006 * Health effects of the chernobyl accident and special health care programs, Reports of the UN Chernobyl Forum Expert Group "Health", 2006, Ed. Bennett et al. Geneva. * PDF Link 概要からの白血病に関する部分の抜粋 太字部は引用者による。 Leukaemia and non-thyroid solid cancer Ionizing radiation is a known cause of certain types of leukaemia (a malignancy of blood cells). An elevated risk of leukaemia was first found among the survivors of the atomic bombings in Japan some two to five years after exposure. Recent investigations suggest a doubling of the incidence of leukaemia among the most highly exposed Chernobyl liquidators. No such increase has been clearly demonstrated among children or adults resident in any of the contaminated areas. 'From the experience of the Japanese bomb survivors it is possible that a large proportion of the leukaemia cases that could be linked to Chernobyl have already occurred, now that 20 years have passed since the accident. However, further studies are needed to clarify this. While scientists have conducted studies to determine whether cancers in many other organs may have been caused by radiation, reviews by the WHO Expert Group revealed no evidence of increased cancer risks, apart from thyroid cancer, that can clearly be attributed to radiation from Chernobyl. Aside from the recent finding on leukaemia risk among Chernobyl liquidators, reports indicate a small increase in the incidence of pre-menopausal breast cancer in the most contaminated areas, which appear to be related to radiation dose. Both of these findings, however, need confirmation in well-designed epidemiological studies. The absence of demonstrated increases in cancer risk – apart from thyroid cancer – is not proof that no increase has occurred. Based on the experience of atomic bomb survivors, a small increase in the risk of cancer is expected, even at the low to moderate doses received. Such an increase, however, is expected to be difficult to identify. 太字部分和訳　最近の研究によれば、最も高い被曝を受けたチェルノブイリの清掃人に二倍の白血病の発症が見出されている。そのような増加は、汚染地域の住人である子供や大人に明確には示されていない。 ---- '白血病に関する部分の抜粋 P55 - Chapter 4 LEUKAEMIA An elevated riskfor leukaemia was recorded among the survivors of the atomic bombings of Hiroshima and Nagasaki (Preston et al., 1994). Ionizing radiation is a well substantiated causal mechanism for leukaemia''' other than chronic lymphoid leukaemia (CLL), with a latency period of 2-5 years following exposure'. Leukaemia has also been associated with occupational exposure to radiation in early radiologists and radiation scientists (Yoshinaga et al., 2004) and radiotherapy for malignant and non-malignant diseases (Ron, 2003). The risk for leukaemia caused by low dose/low dose-rate exposures is not established. In the Utah case-control study on leukaemia in the U.S., a weak association between bone marrow dose from radioactive fallout from the Nevada Nuclear Test Site and all types of leukaemia, all ages, and all time periods after exposure was found (Stevens et al., 1990). In a pooled analysis study of nuclear workers from the U.S., Canada and the U.K., a statistically significant association was found for leukaemia excluding CLL (Cardis et al., 1995). '''Exposure In Utero' Current status of evidence Several ecological studies have addressed the question of leukaemia risk in children who were exposed to Chernobyl fallout while in utero, with conflicting results. A Greek study comparing rates for temporal cohorts born during —exposed“and —unexposed“periods found a 2.6-fold increase in leukaemia riskand elevated rates for those born in regions with higher levels of radioactive fallout (Petridou et al., 1996). However, the numbers of cases in each exposure group were small, and the results could not be duplicated when a similar approach comparing areas with the same categories of contamination (<6 kBq/m^2 , 6-10 kBq/m^2 , >10 2kBq/m^2) was applied to the analysis of data from the German Childhood Cancer Registry (Steiner et al., 1998). In a study in Belarus (Ivanov et al., 1998), where levels of contamination are higher by a factor of 10 or more, the results were similar to the Greek study but the trend was weaker, raising doubt about the role of radiation in the observed increase. Nevertheless, the highest annual incidence rate was in 1987, the year after the accident, and though numbers are small and the results statistically non-significant, the largest rate ratio (RR=1.51; 95% CI 0.63œ 3.61) was found in the two most contaminated regions (Gomel and Mogilev). A more recent small study published by Noshchenko et al. (2001) compares leukaemia incidence during 1986 to 1996 among children born in 1986 and thus exposed in utero in Zhitomir, a contaminated oblast, with children born in Poltava, a supposedly uncontaminated oblast. The reported riskratios based on cumulative incidence show significant increases for all leukaemia (RR=2.7; 95% CI 1.9-3.8) and for the subtype of acute lymphoblastic leukaemia (RR=3.4; 95% CI 1.1-10.4). The small number of cases (21 in Zhitomir, 8 in Poltava) suggests that interpretation of this result must be cautious. An ongoing study, the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) established in 1988 (Parkin et al., 1996), examines risk of leukaemia by age using data from population-based cancer registries in Europe (including Belarus and Ukraine). Focusing on the riskof leukaemia by age of diagnosis (six months intervals) in relation to the estimated preliminary results suggest a small doses from the Chernobyl fallout received in utero, increase in risk in infant leukaemia and leukaemia diagnosed between 24-29 months. Various sensitivity analyses examining potential sources of bias, especially differential availability of day/month of birth and diagnosis, showed a similar increase in risk for the aforementioned age-groups (Loos, 2004). Expert assessment ''' '''Consensus The available evidence from ecological studies is not entirely convincing, particularly in light of the results from Belarus. The statistical power of these studies was low for detecting moderate sized effects, and the exposure assessment measures were quite crude. There are as yet no data from analytical epidemiological studies in which individual dose estimates are available. Thus, there is neither strong evidence for or against an association between in utero exposure to Chernobyl fallout and an increased riskof leukaemia. The hypothesis that low-dose fetal irradiation may damage hematopoiesis processes still seems worth further testing, but primarily on the basis of biological assumptions related to susceptibility rather than to empirical evidence. Based on studies of exposure to x rays (Bithell and Stewart, 1975; Wakeford and Little, 2003), it appears that the prenatal period is one of increased susceptibility to radiation damage. However, few data are available to assess this possibility in the context of the Chernobyl accident, although the observation that those youngest at the time of exposure are at highest riskis suggestive. With respect to the observed temporal patterns, increases seen within 3-5 years of exposure are compatible with leukaemia increases in other exposure circumstances, including at Hiroshima and Nagasaki. Study of atomic-bomb survivors found increases in risk among those exposed in utero (Yoshimoto et al., 1991), but t'here was low power to evaluate whether the in utero period is more or less radiosensitive than the early postnatal period. '''Moreover, the exposure involved a substantially higher dose and dose rate.' At the Nevada test site the numbers of cases among the in utero exposed were also too few to evaluate risk (Stevens et al., 1990). '''Gaps in knowledge The primary gaps in knowledge from the epidemiological point of view relate to the complete absence of analytical studies in which dose and risks are estimated at the individual level. However, because of the relatively small doses, and rarity of leukaemia as an outcome, it is not clear that such studies would have sufficient statistical power to yield meaningful results. Recommendations We know of no ongoing studies of in utero exposure and leukaemia risk. We recommend an extension of existing or planned analytical studies of childhood leukaemia to collect the necessary data to allow for the analysis of in utero exposure. Exposure of Children Current status of evidence Several ecological epidemiological studies have examined the association between radiation exposure to children from Chernobyl and the occurrence of leukaemia. The European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) is one of the largest and most comprehensive to date. This study utilized incidence data in children under age 15 from 36 cancer registries in 23 countries. Average radiation doses were calculated based on estimates of environmental contamination and consumption of contaminated foodstuffs. Parkin et al. (1993) compared acute leukaemia incidence rates before the Chernobyl accident (1980-1985) with those for the years 1987 and 1988. Although the number of leukaemia cases for 19871988 significantly exceeded the number of cases expected on the basis of 1980-1985 data, there was no evidence that the excess in leukaemia rates was more pronounced in areas that were most affected by Chernobyl-related ionizing radiation exposure. Similar results were observed in the 5-year ECLISfollow-up report (Parkin et al., 1996). Additional reports have focused on changes in childhood leukaemia rates before and after the accident in individual European countries and elsewhere. Overall, there was little evidence for an increase in rates of childhood leukaemia in Ukraine (Prisyazhiuket al., 1991), Belarus (Ivanov et al., 1993; Gapanovich et al., 2001), Russia (Ivanov, 2003; Ivanov and Tsyb, 2002; Ivanov et al., 2003c) This citation is somehow screwed up, since in the referece list there are three Ivanov papers in 2003, and two of them overlap. the other one (Ivanov, Gorski, Tsyb Maksioutov BNJ article is about liquidators. ), Finland (Auvinen et al., 1994), Sweden (Hjalmars, Kulldorff, and Gustafsson, 1994; Tondel et al., 1996), or Greece (Petridou et al., 1994; 1996) after the Chernobyl accident. Furthermore, there was no association between the extent of contamination and the increase in risk in these countries. However, one Swedish study (Hjalmars et al., 1994) reported a non-statistically significant yet suggestive increase of acute lymphocytic leukaemia riskin children younger than 5 at the time of exposure (OR 1.5; 95% CI 0.8œ2.6). A small study in northern Turkey showed that in one pediatric cancer treatment center, more patients with acute lymphocytic leukaemia were seen after the accident than before, but no incidence rates were reported (Gunay, Meral, and Sevinir, 1996). There has been only one analytical (case-control) study of childhood leukaemia reported to date (Noshchenko et al., 2002), '''based on cases identified among residents of the Rivno and Zhytomir oblasts in Ukraine. Cases were under age 20 at the time of the accident and were diagnosed between 1987 and 1997. Data were collected on 272 cases, however, the analysis was based on only 98 cases that were independently verified and interviewed. Controls were randomly selected from the same oblasts, excluding the raion of residence of the case, and matched according to age at the time of the accident, gender, and type of settlement. The mean estimated dose to the bone marrow among study subjects was 4.5 mSv and the maximum was 101 mSv. The study found a statistically significant increased risk of acute leukaemia among males with cumulative doses above 10 mSv and diagnosed from 1993-1997. A similar association was found for acute myeloid leukaemia diagnosed in the period 1987-1992. These results should be interpreted cautiously, however, as they are based on approximately only one-third of the cases and a lesser proportion of controls, and it is not clear whether cases and controls were selected for dose estimation in an unbiased manner. There are several ongoing studies of childhood exposure and leukaemia for which results are not currently available. These include:* International Consortium for Research on the Health Effects of Radiation case-control study of childhood leukaemia in Ukraine, Belarus, and Russia.* Franco-German study of leukaemia incidence in children in Bryanskand Kaluga ñ Franco-German study of leukaemia incidence in children in several oblasts in Ukraine. 'Expert assessment ' 'Consensus ' On balance, the existing evidence does not support the conclusion that rates of childhood leukaemia have increased as a result of radiation exposures from the Chernobyl accident. However, ecological studies of the types conducted to date are not particularly sensitive to detecting relatively small changes in the incidence of a disease as uncommon as childhood leukaemia over time or by different geographical areas. Further, existing descriptive studies vary in several aspects of study design:methods of case ascertainment (cancer registries versus retrospective record review), methods of classifying radiation exposure, and length of follow up after the accident (range 2-10 years). The single analytical study is insufficient to draw convincing conclusions regarding leukaemia risk among children after Chernobyl exposure.' '''Gaps in knowledge' As yet, there is no convincing evidence to demonstrate a measurable increase in risk of leukaemia following childhood exposure from Chernobyl. Thus, the primary gap in knowledge is the existence or nonexistence of a measurable risk. Other factors such as the dose-response relationship, the effect of protracted exposure, potential modifying effects of age at exposure and time since exposure are also unknown, and study of such effects is contingent upon the basic demonstration of a measurable risk. However, the statistical power for testing for a measurable association will generally be low, and the power for modifying effects will be lower still. Recommendations Incidence rates for childhood leukaemia in populations exposed to Chernobyl radiation should continue to be monitored in order to detect increases that may still occur. Properly designed and executed analytical epidemiological studies with individual dose measurements and individual risk estimation should be encouraged, as these will give the most definitive results with respect to this important issue. ---- References Auvinen et al. (1994) Fallout from Chernobyl and incidence of childhood leukaemia in Finland, 1976-92. BMJ. 1994 Jul 16;309(6948):151-4. PubMed PMID: 8044092; PubMed Central PMCID: PMC2540671. http://www.ncbi.nlm.nih.gov/pubmed/8044092 Bithell & Stewart (1975) Pre-natal irradiation and childhood malignancy: a review of British data from the Oxford Survey. Br J Cancer. 1975 Mar;31(3):271-87. PubMed PMID: 1156514; PubMed Central PMCID: PMC2009418. http://www.ncbi.nlm.nih.gov/pubmed/1156514 Cardis et al. (1995) Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Radiat Res. 1995 May;142(2):117-32. 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